New research from University College Cork, Ireland has revealed that the gut microbiota plays a critical role in managing stress responses by regulating the body’s circadian rhythms. The study shows how the natural oscillations of gut microbes influence stress hormone release and stress-sensitive behaviours at different times of day, highlighting the powerful connection between gut health and mental well-being.
The researchers observed that depleting gut microbes in mice, either through antibiotics or in germ-free conditions, disrupted the daily rhythms of corticosterone, a key stress hormone. Without gut microbes, the mice showed increased levels of corticosterone and a breakdown in the regular, rhythmic activity of genes controlling stress responses in the hypothalamus, pituitary, and adrenal glands. These changes were also linked to altered behaviours, with microbe-depleted mice displaying atypical responses to stress compared to their microbe-rich counterparts.
The study underscores the significance of the hypothalamic-pituitary-adrenal (HPA) axis, which coordinates stress and circadian responses. Researchers found that the disruption of microbial rhythms affected not only hormone secretion but also the brain’s transcriptome and metabolome, resulting in hyper-activation of the HPA axis at certain times of day, especially during sleep-to-wake transitions. This disruption led to abnormal responses to stress and impaired social interactions.
A particularly intriguing finding was the role of specific gut bacteria, notably Limosilactobacillus reuteri, which appeared essential for the normal, rhythmic secretion of stress hormones. Restoring gut microbiota restored typical stress responses, supporting the potential of microbiota-based therapies to promote mental well-being by aligning with the body’s natural clock.
As modern life increasingly disrupts circadian patterns, this research emphasises the importance of maintaining a balanced microbiome to support natural stress responses, paving the way for potential therapeutic strategies targeting stress-related disorders through the gut microbiota.
Reference
Tofani GSS et al. Gut microbiota regulates stress responsivity via the circadian system. Cell Metab. 2024;DOI:10.1016/j.cmet.2024.10.003.